Tumor-associated neutrophil extracellular
traps (NETs) play a critical
role in promoting tumor growth and assisting tumor metastasis. Herein,
a smart nanocarrier (designated as mP-NPs-DNase/PTX) based on regulating
tumor-associated NETs has been developed, which consists of a paclitaxel
(PTX) prodrug nanoparticle core and a poly-l-lysine (PLL)
conjugated with the matrix metalloproteinase 9 (MMP-9)-cleavable Tat-peptide-coupled
deoxyribonuclease I (DNase I) shell. After accumulating at the site
of the tumor tissue, the nanocarrier can release DNase I in response
to MMP-9 to degrade the structure of NETs. Then, the remaining moiety
can uptake the tumor cells via the mediation of exposed
cell penetrating peptide, and the PTX prodrug nanoparticles will lyse
in response to the high intracellular concentration of reduced glutathione
to release PTX to exert a cytotoxic effect of tumor cells. Through in vitro and in vivo evaluations, it has
been proven that mP-NPs-DNase/PTX could serve as potential NET-regulated
nanocarrier for enhanced inhibition of malignant tumor growth and
distant metastasis.
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